A new NMR approach has been developed to measure ultraprecise distance and orientational information in proteins. The so-called cross-correlated magnetization transfer, carried out in a quantitative fashion, relies on interference between 1H-1H and 1H-13C dipolar interactions. The magnitude of the effect scales with the inverse sixth power of the interproton distance, and in contrast to NOE distance information, it is essentially insensitive to indirect effects. Comparison of rates measured in the third Igg-binding domain of protein G, for which a 1.1-A resolution X-ray structure is available, shows quite good agreement, which nevertheless remains limited by the coordinate accuracy of the crystal structure. Comparison of rates measured for HIV protease, for which multiple 1.8-A X-ray structures are available, shows considerably poorer agreement, but agreement among predicted rates for the crystal structures is even poorer, indicating that the coordinate uncertainty in these structures is high, and that inclusion of the cross correlation rates in refinement of structures should yield considerable improvements in coordinate accuracy. Measurement of anisotropic interactions in weakly aligned proteins remains a main focus of our work. Improvements in alignment methodology have been developed, including the introduction of anisotropically compressed charged acrylamide gels. These gels are compatible with detergent, and comparison of the structure of an HIV gp41 peptide solubilized either in detergent or by disk-shaped micelles shows that in both cases the peptide is alpha-helical, but solubilization by detergent micelles yields strong curvature of the helix axis, whereas the use of flat micelles yields essentially straight helices. More effective methods for measurement of 1H-1H dipolar interactions in aligned proteins have also been developed, and interactions over distances exceeding 7 A have been demonstrated. It is anticipated that this approach will be useful for the study of larger, perdeuterated systems.